Two-component regulatory systems are ubiquitous in bacteria and offer potential targets for the development of antibacterial drugs. A molecular level understanding of how a membrane bound sensor kinase autophosphorylates in response to an input signal, selectively binds and phosphorylates its response regulator, and the activated response regulator subsequently elicits the appropriate cellular function, is central to engineering pharmaceutical interventions. Focusing on the response regulator; we propose to determine the structural mechanism by which the event of receiver domain phosphorylation results in the activation of the DNA binding domain of the response regulator NarL through the application of high resolution NMR techniques. This will be accomplished by first solving the structures of the isolated receiver and DNA binding domains which we have shown, remain structured in solution. We will also determine the structural changes involved in phosphorylating the receiver domain, binding target DNA to the DNA binding domain, and adding the two domains in trans. Our ultimate goal will be to compare the complete NMR structures of the resting state and the active state of full length NarL.